Adrenomedullin and adrenomedullin binding protein-1 prevent acute lung injury after gut ischemia-reperfusion.
J Am Coll Surg
; 205(2): 284-93, 2007 Aug.
Article
em En
| MEDLINE
| ID: mdl-17660075
ABSTRACT
BACKGROUND:
Ischemic bowel remains a critical problem, resulting in up to 80% mortality. Acute lung injury, a common complication after intestinal ischemia/reperfusion (I/R), might be responsible for such a high mortality rate. Our previous studies have shown that administration of a novel vasoactive peptide adrenomedullin (AM) and its binding protein (AMBP-1) reduces the systemic inflammatory response in rat models of both hemorrhage and sepsis. It remains unknown whether administration of AM/AMBP-1 has any protective effects on intestinal I/R-induced acute lung injury. We hypothesized that administration of AM/AMBP-1 after intestinal I/R prevents acute lung injury through downregulation of proinflammatory cytokines. STUDYDESIGN:
Intestinal I/R was induced by placing a microvascular clip across superior mesenteric artery (SMA) for 90 minutes in adult male Sprague-Dawley rats (275 to 325 g). On release of the SMA clamp, the animals were treated with either AM (12 mug/kg body weight) in combination with AMBP-1 (40 microg/kg body weight) or vehicle (1 mL normal saline) during a period of 30 minutes through a femoral vein catheter. Lung samples were collected at 4 hours after treatment or sham operation. Lung injury was assessed by examining lung water content, morphologic changes, and granulocyte myeloperoxidase activity. Tumor necrosis factor-alpha and interleukin-6 gene expression and their protein levels in the lungs were measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. In additional groups of animals, AM/AMBP-1 or vehicle was administered at 1 hour after onset of reperfusion. Lung histology was examined at 3 hours after treatment.RESULTS:
Intestinal I/R induced considerable lung injury, as characterized by lung edema, histopathologic changes, increased myeloperoxidase activity, and proinflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) levels in the lungs. Administration of AM/AMBP-1 after ischemia mitigated lung injury and dramatically downregulated proinflammatory cytokines. Lung injury was also ameliorated by delayed AM/AMBP-1 treatment as evidenced by improvement in lung histology.CONCLUSIONS:
AM/AMBP-1 can be developed as a novel treatment to attenuate acute lung injury after an episode of gut ischemia. The protective effect of AM/AMBP-1 appears to be mediated through downregulation of proinflammatory cytokines.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome do Desconforto Respiratório
/
Vasodilatadores
/
Traumatismo por Reperfusão
/
Fator H do Complemento
/
Adrenomedulina
/
Intestinos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Am Coll Surg
Assunto da revista:
GINECOLOGIA
/
OBSTETRICIA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos